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Kouichiro Minami

Publications and source records attributed to Kouichiro Minami.

48 records · Page 3Linked to original sources
PubMed2002

Tramadol has no effect on cortical renal blood flow--despite increased serum catecholamine levels--in anesthetized rats: implications for analgesia in renal insufficiency.

UNLABELLED: Tramadol is an analgesic that inhibits norepinephrine (NE) reuptake. Although NE released from renal sympathetic nerves causes renal hypoperfusion, the effects of tramadol on renal hemodynamics have not been well characterized. We investigated the effects of tramadol on renal blood flow (RBF), mean arterial blood pressure (MAP), and heart rate (HR) by using a laser Doppler flowmeter, both in normal anesthetized rats and in rats with experimentally-induced nephritis secondary to anti-Thy 1.1 antibody administration. We also studied the effects of tramadol on serum NE levels. Tramadol increased MAP and decreased HR without changing RBF in normal rats at clinical doses. Serum NE levels increased up to 176% of control after a 2 mg/kg bolus injection of tramadol. Continuously infused, increasing doses of tramadol (0.5-4 mg.kg(-1).h(-1)) did not affect MAP, HR, or RBF. Tramadol also increased MAP and decreased HR without changing RBF in rats with experimentally induced renal insufficiency. These findings suggest that a bolus injection of tramadol does not alter RBF, although it causes a decrease in HR and an increase in MAP and serum NE in both normal rats and in rats with renal insufficiency. These results suggest that tramadol may have little effect on RBF during the postoperative period. IMPLICATIONS: A bolus and continuous injection of tramadol does not alter renal blood flow (RBF) in normal rats. A bolus injection of tramadol has little effect on RBF in rats with experimentally induced renal insufficiency. These results suggest that tramadol would be a safe analgesic for maintaining RBF during the postoperative period.

Analgesia↗
PubMed2002

Tramadol inhibits norepinephrine transporter function at desipramine-binding sites in cultured bovine adrenal medullary cells.

UNLABELLED: Tramadol is a widely used analgesic, but its mode of action is not well understood. To study the effects of tramadol on norepinephrine transporter (NET) function, we assayed the effect of tramadol on [3H]-norepinephrine ([3H]-NE) uptake and [3H]-desipramine binding to plasma membranes isolated from bovine adrenal medulla. We then characterized [14C]-tramadol binding in cultured bovine adrenal medullary cells. Tramadol inhibited the desipramine-sensitive uptake of [3H]-NE by the cells in a concentration-dependent manner (50% inhibitory concentration = 21.5 +/- 6.0 microM). Saturation analysis revealed that tramadol increased the apparent Michaelis constant of [3H]-NE uptake without changing the maximal velocity, indicating that inhibition occurred via competition for the NET (inhibition constant, K(i) = 13.7 microM). Tramadol inhibited the specific binding of [3H]-desipramine to plasma membranes. Scatchard analysis of [3H]-desipramine binding revealed that tramadol increased the apparent dissociation constant (K(d)) for binding without altering maximal binding, indicating competitive inhibition (K(i) = 11.2 microM). The binding of [14C]-tramadol to the cells was specific and saturable, with a K(d) of 18.1 +/- 2.4 microM. These findings indicate that tramadol competitively inhibits NET function at desipramine-binding sites. IMPLICATIONS: Tramadol competitively inhibits norepinephrine transporter function at desipramine-binding sites in the adrenal medullary cells and probably the noradrenergic neurons of the descending inhibitory system.

Adrenal Medulla↗
PubMed2002

A neurosteroid anesthetic, alphaxalone, inhibits nicotinic acetylcholine receptors in cultured bovine adrenal chromaffin cells.

UNLABELLED: Several lines of evidence suggest that nicotinic acetylcholine receptors (nAChRs) are a target of general anesthetics. Alphaxalone (5alpha-pregnan-3alpha-ol-11, 20-dion) is a neurosteroid, which was used clinically for anesthesia, but its effects on the function of nAChRs have not been well investigated. We examined the effects of alphaxalone on nAChRs in cultured bovine adrenal chromaffin cells. We studied the effects of alphaxalone on nicotine-induced increases in the cytosolic Ca(2+) concentration ([Ca(2+)](i)) and on membrane currents using Ca(2+)-imaging and whole-cell patch-clamp techniques, respectively, in these cells. We also examined the effects of alphaxalone on gamma-aminobutyric acid A receptors in the same cells and compared them with the effects on nAChRs. Alphaxalone (0.1-100 micro M) inhibited nicotine-induced [Ca(2+)](i) increases in a concentration-dependent manner. Alphaxalone inhibited high K(+)-induced [Ca(2+)](i) increases, but the inhibition was observed only at 100 micro M. In voltage-clamp experiments using negative holding potentials, alphaxalone (0.1-100 micro M) itself induced inward currents, which were abolished by the gamma-aminobutyric acid A receptor antagonist picrotoxin. Alphaxalone also inhibited nicotine-induced inward currents, and the inhibition was unaffected by picrotoxin. We conclude that alphaxalone, at anesthetic concentrations, inhibits nAChRs in adrenal chromaffin cells. Alphaxalone may affect the sympathetic and other nervous systems via inhibition of nAChRs. IMPLICATIONS: Alphaxalone inhibits the function of nAChRs at clinically relevant concentrations in adrenal chromaffin cells. Thus, the present findings may provide some information for understanding the anesthetic mechanism of alphaxalone.

Anesthetics↗
PubMed2002

The inhibitory effects of tramadol on muscarinic receptor-induced responses in Xenopus oocytes expressing cloned M(3) receptors.

UNLABELLED: Tramadol is a widely used analgesic, but its mechanism of action is not completely understood. Muscarinic receptors are involved in neuronal function in the brain and autonomic nervous system, and much attention has been paid to these receptors as targets of analgesic drugs in the central nervous system. In this study, we investigated the effects of tramadol on type-3 muscarinic (M(3)) receptors using the Xenopus oocyte expression system. Tramadol (10 nM-100 micro M) inhibited acetylcholine-induced currents in oocytes expressing M(3) receptor. Although GF109203X, a protein kinase C inhibitor, increased the basal current, it had little effect on the inhibition of acetylcholine-induced currents by tramadol. Moreover, tramadol inhibited the specific binding sites of [(3)H]quinuclidinyl benzilate. These findings suggest that tramadol at clinically relevant concentrations inhibits M(3) function via quinuclidinyl benzilate-binding sites. This may explain the modulation of neuronal function and the anticholinergic effects of tramadol. IMPLICATIONS: Muscarinic receptors are involved in neuronal function and are targets of analgesic drugs. We here report that tramadol inhibits type-3 muscarinic receptors function via quinuclidinyl benzilate-binding sites at clinically relevant concentrations. These findings may explain the modulation of neuronal function and the anticholinergic effects of tramadol.

Acetylcholine↗
PubMed2002

Alphaxalone, a neurosteroid anesthetic, inhibits norepinephrine transporter function in cultured bovine adrenal medullary cells.

UNLABELLED: We studied the effects of alphaxalone, a neurosteroid anesthetic, on norepinephrine transporter (NET) function in cultured bovine adrenal medullary cells and the effect of a bolus injection of alphaxalone on blood pressure and serum norepinephrine (NE) levels in anesthetized rats. Alphaxalone (10-100 micro M) inhibited the desipramine-sensitive uptake of [(3)H]-NE by bovine adrenal medullary cells in a concentration-dependent manner. Eadie-Hofstee analysis of [(3)H]-NE uptake showed that alphaxalone increased the apparent Michaelis constant without altering the maximal velocity, indicating that inhibition occurred via competition for the NET. Alphaxalone inhibited the specific binding of [(3)H]-desipramine to plasma membranes isolated from bovine adrenal medulla. Scatchard analysis of [(3)H]-desipramine binding revealed that alphaxalone increased the apparent dissociation constant for binding without altering maximal binding, indicating competitive inhibition. Bolus IV administration of alphaxalone had little effect on blood pressure but slightly, and significantly, increased the serum NE levels in anesthetized rats. These findings suggest that alphaxalone competitively inhibits NET function by interfering with both desipramine binding and NE recognition on the NET in adrenal medullary cells and probably in sympathetic neurons. IMPLICATIONS: Alphaxalone inhibited the desipramine-sensitive uptake of [(3)H]-norepinephrine (NE) by interfering with desipramine binding in bovine adrenal medullary cells. A bolus IV administration of alphaxalone slightly and significantly increased the serum NE levels in anesthetized rats. These findings suggest that alphaxalone competitively inhibits NE transporter function probably in sympathetic neurons.

Adrenal Medulla↗
PubMed2002

Inhibitory effects of ethanol on rat mesangial cell proliferation via protein kinase C pathway.

A large body of evidence has shown that ethanol inhibits the cell growth and cell proliferation in a variety of cell types. However, it has not been studied whether ethanol inhibits the proliferation of mesangial cells (MC) in the kidney. We examined the effects of ethanol on cell proliferation in cultured rat MC. Treatment with ethanol (10-200 mM) for 48 hr inhibited [(3)H]thymidine incorporation into MC in a concentration-dependent manner. The same concentrations of ethanol also inhibited the increase in cell number of MC. GF109203X and chelerythrine chloride, inhibitors for protein kinase C, eliminated the inhibitory effects of ethanol; and protein kinase C activator, PMA, mimicked the effects of ethanol. In contrast, neither the protein kinase A inhibitor H-89 nor the protein kinase G inhibitor KT5823 had any effect. These findings suggest that ethanol has inhibitory effects on the proliferation of MC, probably via activation of the protein kinase C pathway.

Animals↗
PubMedDate not supplied

Intramuscular tramadol increases gastric pH during anesthesia.

PURPOSE: Tramadol, [(1RS, 2RS)-2-dimethylamino) methyl-1-(3-methoxyphenyl)-cyclohexanol hydrochloride], is an analgesic in clinical use. It has been reported that tramadol inhibits muscarinic type 3 receptor function, which primarily mediates smooth muscle contraction and glandular secretion. We investigated the effects of tramadol on the pH of gastric juices during anesthesia to determine whether tramadol inhibits secretion from the gastric glands. METHODS: ASA physical status I or II adult patients (n = 30) presenting for major elective orthopedic surgery of the upper extremities or mastectomy were enrolled. Patients were randomly assigned to receive treatment with tramadol (n = 10), famotidine (n = 10), or saline (n = 10). General anesthesia was then induced using propofol, vecuronium bromide, and fentanyl. After inducing anesthesia, the gastric pH was measured using pH test paper and, then, 100 mg tramadol, 20 mg famotidine, or saline were injected into the deltoid muscle. Three hours after starting the operation, gastric juice was again aspirated and its gastric pH measured. RESULTS: There were no differences in the pH before anesthesia between the three groups. By contrast, gastric pH was increased in the tramadol group by the same amount as it was in the famotidine group three hours after administering the drugs. Gastric pH of the saline, famotidine, and tramadol groups was 2.6 +/- 2.5, 6.3 +/- 2.0, and 6.4 +/- 0.8, respectively. CONCLUSION: These results suggest that tramadol inhibits the secretion of gastric acid.

Adult↗